Color Atlas of Neurology (Thieme 2004)

Nonepileptic Seizures

according to the ICD-10). Epileptic seizures in family members, or in the patients themselves, may serve as the prototype for psychogenic seizures.

Premonitory signs. Psychogenic seizures can be induced or terminated by suggestion. They may be preceded by a restless, anxious, or fearful state. They usually occur in the presence of others (an “audience”) and do not occur when the patient is asleep.

Seizure semiology. Psychogenic seizures usually take a dramatic course, with a variable ending. Their semiology is usually of a type more likely to incite sympathy and pity in onlookers than fear or revulsion. Typical features include an abrupt fall or slow collapse, jerking of the limbs, tonic contraction of the body, writhing (arc de cercle), calling out, shouting, rapid twisting of the head and body, and forward pelvic thrusting; the sequence of movements is usually variable. The eyes are usually closed, but sometimes wide open and staring; the patient squeezes the eyes shut when passive opening is attempted. Urinary incontinence or injury (self-mutilation) may also occur. Tongue-bite injuries, if present, are usually at the tip of the tongue (those in true epileptic fits are usually lateral). The patient is

202less responsive than normal to external stimuli, including painful stimuli, but not unconscious

(squeezes eyelids shut when the eyes are

touched, drops arm to the side when it is held over the patient’s face and released). The patient’s skin is not pale or cyanotic during the ictus. Patients who hyperventilate during psychogenic seizures may have carpopedal spasms. Psychogenic seizures often last longer than epileptic seizures.

Postictal phase. No focal neurological deficits can be detected, though there may be a psychogenic postictal stupor. The serum prolactin level is not elevated (which, however, does not rule out a true epileptic seizure). The seizure may be terminated abruptly by suggestion, or by departure of the “audience.” Some patients recall the seizure to some extent, while others emphatically deny memory of it.

! Panic Disorder (ICD-10 F41.0)

Panic disorder is characterized by sudden, unexpected and apparently unprovoked attacks of intense anxiety, which may range in severity from a general feeling of restlessness to a mortal dread. The attacks usually last 5–30 minutes and may awaken the patient from sleep. Accompanying symptoms include feelings of detachment from the environment, i.e., depersonalization (detachment from one’s own body, floating state) and derealization (sensation of being in a dream or nightmare, feeling of unreality); autonomic and other physical symptoms of variable severity, including cardiovascular (tachycardia, palpitations, pallor, chest pain or pressure), gastrointestinal (nausea, dry mouth, dysphagia, diarrhea), respiratory (hyperventilation, dyspnea, smothering sensation), and other manifestations (tremor, twitching of the limbs, dizziness, paresthesia, mydriasis, urinary urgency, sweating). The differential diagnosis includes epilepsy (aura, simple partial seizures), hyperthyroidism, hyperventilation syndrome, pheochromocytoma, heart disease, and hypoglycemia.

Nonepileptic Seizures

Panic attack (hyperventilation, psychomotor restlessness)

Central Nervous System

203

Central Nervous System

204

Drop attack

Nonepileptic Seizures

Central Nervous System

Hyperventilation

Central Nervous System

206

Micrographia

Central Nervous System

207

Parkinson Disease: Clinical Features

! Autonomic Dysfunction

Blood pressure changes. Hypotension is a common side effect of antiparkinsonian medications (levodopa, dopamine agonists). Marked orthostatic hypotension, if present, suggests the possible diagnosis of multisystem atrophy.

Constipation may be caused by autonomic dysfunction, as a manifestation of the disease, or as a side effect of medication (anticholinergic agents).

Bladder disorders. Polyuria, urinary urgency, and urinary incontinence occur mainly at night and in patients with severe akinesia (who have difficulty getting to the toilet). PD only rarely causes severe bladder dysfunction.

208Sleep disorders. PD commonly causes disturbances of the sleep–wake cycle, including diffi-

culty falling asleep, nocturnal breathing prob-

lems similar to sleep apnea syndrome, and shortening of the sleep cycle. Sleep may also be interrupted by nocturnal akinesia, which makes it difficult for the patient to turn over in bed.

Sexual dysfunction. Spontaneous complaints of diminished libido or impotence are rare. Increased libido is a known side effect of levodopa and dopamine agonists.

Hyperhidrosis. Mainly occurs as generalized, irregular, sudden episodes of sweating. Seborrhea. Mainly on the forehead, nose, and scalp (greasy face, seborrheic dermatitis).

Leg edema is often the result of physical inactivity.

! Sensory Manifestations

Pain in the arm or shoulder, sometimes accompanied by fatigue and weakness, may be present for years before the cardinal manifestations arise and enable a diagnosis of PD. Back pain and nuchal cramps are frequent secondary effects of parkinsonian rigidity and abnormal posture. Dystonia may also come to attention because of the pain it produces.

Dysesthesia. Heat, burning or cold sensations may be felt in various parts of the body. For restless legs syndrome, see p. 114.

! Other Motor Manifestations

Dystonia. Tonic dorsiflexion of the big toe with extension or flexion of the other toes may occur in the early morning hours or during walking. Dystonia may be drug-induced (e. g., by levodopa) or due to the disease itself. The differential diagnosis includes dopa-responsive dystonia (a disorder of autosomal dominant inheritance) and Wilson disease (p. 307), two predominantly dystonic motor disorders with onset in childhood and adolescence.

Visual disturbances are caused by impairment of eye movement. Vertical gaze palsy is suggestive of progressive supranuclear palsy (p. 302). The reduced blinking rate of PD may lead to a burning sensation on the cornea, or to conjunctivitis.

Seborrhea

Orthostatic hypotension

Constipation

Urinary dysfunction, impotence

(depression, anxiety, dementia)

Autonomic dysfunction

Dystonia (of foot)

Sleep disorders

(increased rigidity at night, ”mental pillow”)

Pain

Central Nervous System

209

Parkinson Disease: Pathogenesis

Neurotransmitters. Glutamate mediates excitatory impulses from the cortex, amygdala, and hippocampus to the striatum. Synapses from STN fibers onto cells of the GPi and SNr are also glutamatergic. Both the excitatory and the inhibitory projections of the SNc to the basal ganglia are dopaminergic. In the striatum, dopamine acts on neurons bearing D1 and D2 receptors, of which there are various subtypes (D1 group: d1, d5; D2 group: d2, d3, d4). D1 receptors predominate in the direct pathway, D2 receptors in the indirect path-

210way. Cholinergic interneurons in the striatum form a relay station within the basal ganglia

(transmitter: acetylcholine). Medium spiny-type

neurons (MSN) in the striatum have inhibitory projections to the GPe, GPi, and SNr (transmitters: GABA, substance P/SP, enkephalin/Enk). Other inhibitory GABAergic projections run from the GPi to the STN, from the GPi to the thalamus (ventrolateral and ventroanterior nucleus), and from the SN to the thalamus. The thalamocortical projections are excitatory.

Motor function. The direct pathway is activated by cortical and dopaminergic projections to the striatum. The projection from the striatum in turn inhibits the GPi, diminishing its inhibitory output to the thalamic nuclei (i.e., causing net thalamic activation). Thalamocortical drive thus facilitates movement initiated in the cerebral cortex (voluntary movement). In the indirect pathway, the striatum, under the influence of afferent cortical and dopaminergic projections, exerts an inhibitory effect on the GPe and STN. The result is a diminished excitatory influence of the STN on the GPi and SNr, ultimately leading to facilitation of cortically initiated voluntary movement and inhibition of involuntary movement.

! Pathophysiology

The cause of Parkinson disease is unknown. Its structural pathological correlate is a loss of neurons in the caudal and anterolateral parts of the SNc, with reactive gliosis and formation of Lewy bodies (eosinophilic intracytoplasmic inclusions in neurons) and Lewy neurites (abnormally phosphorylated neurofilaments) containing α- synuclein. Loss of pigment in the substantia nigra can be seen macroscopically. The most prominent neurochemical abnormality is a deficiency of dopamine in the striatum, whose extent is directly correlated with the severity of PD. The physiological effect of the lack of (mostly inhibitory) dopamine neurotransmission in the striatum is a relative increase in striatal activity, in turn causing functional disinhibition of the subthalamic nucleus via the indirect pathway. Meanwhile, in the direct pathway, decreased striatal inhibition of the GPi enhances the inhibitory influence of the GPi on the thalamus, leading to reduced activity in the thalamocortical projection. These changes in neural activity manifest themselves in the clinically observable akinesia, rigidity, and postural instability. For tremor, see p. 62.